Prostate cancer is a malignant disease that is observed in men. A large number of patients suffer from prostate cancer in the United States and Europe. In recent years, the number of patients who suffer from prostate cancer has rapidly increased in Japan. Since prostate cancer grows slowly, and may effectively be treated by radiotherapy or anti-androgenic therapy, it is important to find prostate cancer in an early stage.
Prostate-specific antigen (hereinafter may be referred to as “PSA”) is a glycoprotein (serine protease) that is secreted from prostate epithelial cells, and has a molecular weight of 33,000 to 34,000 Da. Since a person who suffers a prostate disease shows an increase in PSA level in blood as compared with a healthy person, PSA is useful for early detection of a prostatic disease (particularly prostate cancer). PSA is classified into complex-type PSA that binds to a protease inhibitor in blood, and free PSA (hereinafter may be referred to as “fPSA”). Most of the PSA in blood is complex-type PSA, and present as complex of PSA and α1-antichymotrypsin (hereinafter may be referred to as “PSA-ACT”), complex of PSA and α2-macroglobulin, or the like. fPSA and PSA-ACT can be measured by an immunoassay.
An assay based on agglutination (immunoagglutination assay) that utilizes a latex or the like is used as the immunoassay. However, since an anti-PSA monoclonal antibody has different reactivity with fPSA and PSA-ACT, it may be difficult to accurately measure the total PSA level.
In order to solve the above problem, PTL 1 proposes an immunoagglutination assay reagent and an assay that utilizes the same, wherein the immunoagglutination assay reagent including (1) a first particle suspension that includes first insoluble carrier particles immobilizing thereon a first monoclonal antibody that can bind to a free measurement target substance and a complex of the free measurement target substance and the corresponding binding molecule, (2) a second particle suspension that includes second insoluble carrier particles immobilizing thereon a second monoclonal antibody that can bind to the free measurement target substance and a complex of the free measurement target substance and the corresponding binding molecule, and does not compete with the first monoclonal antibody, and (3) a third particle suspension that includes third insoluble carrier particles immobilizing thereon a third monoclonal antibody that does not recognize the free measurement target substance, but recognizes a complex of the free measurement target substance and the corresponding binding molecule.
PTL 2 proposes an assay reagent and an assay that utilizes the same, wherein the assay reagent adjusting reactivity with a free antigen and a complex-type antigen by using carriers having a smaller particle size among two or more types of carriers that differ in particle size and immobilizing thereon at least one monoclonal antibody among three monoclonal antibodies that have reactivity with a free antigen and a complex-type antigen and differ in recognition site, and using carriers having a larger particle size among the two or more types of carriers and immobilizing thereon the remaining monoclonal antibodies.
PTL 3 proposes a two-step reaction immunoassay that includes (1) reacting a sample that includes a free measurement target substance and a complex-type measurement target substance with a latex 1 on which a monoclonal antibody 1 to the measurement target substance is immobilized to obtain a reaction product 1, and (2) reacting the reaction product 1 with a latex 2 on which a monoclonal antibody 2 that differs in recognition site from the monoclonal antibody 1 is immobilized to obtain a reaction product 2.
PTL 4 proposes a prostate-specific antigen immunoassay reagent and an assay that utilizes the same, wherein the immunoassay reagent including a latex 1 on which a monoclonal antibody 1 that has reactivity with free PSA and PSA complex is immobilized, and a latex 2 on which a monoclonal antibody 2 that has reactivity with free PSA and PSA complex is immobilized, the monoclonal antibody 2 differing in recognition site from the monoclonal antibody 1, and the latex 2 differing in average particle size from the latex 1.